Cognition Therapeutics Inc.'s mission is to develop effective therapeutics for Alzheimer's, Mild Cognitive Impairment and Down's syndrome. Recent scientific discoveries in the Alzheimer's disease field have identified oligomers of the brain protein Abeta 42 as toxic culprits in the disease process. Drugs that antagonize the binding of this toxic protein to neuronal receptors and block the downstream pathological signaling that inhibits memory formation should prevent further damage, and unmask existing memory capacity as synapses recover. Drugs that stop oligomer-induced damage are therefore hypothesized to be disease-modifying treatments that would be effective throughout the course of the disease, and significantly impact the lives of the millions of Alzheimer's patients. Pharmaceutical industry efforts targeted specifically at oligomer blockade are currently limited. Cognition Therapeutics is one of the only companies uniquely focused on discovery of small molecule receptor antagonists of toxic soluble oligomers. We have discovered a CNS drug-like lead series of oligomer receptor antagonists, CT0093. Analogs in this series reduce binding of oligomers to synapses and completely block Abeta oligomer-induced membrane trafficking changes and synapse loss. CT0093 also completely blocks oligomer-induced memory deficits in Alzheimer's disease mouse models. This proposal will allow us to expand our preliminary medicinal chemistry analoging efforts and optimize the CT0093 molecular scaffold with the goal of obtaining a disease-modifying IND candidate drug.